Enhanced Deep-Learning Model for Carbon Footprints of Chemicals.

Millions of chemicals have been designed; however, their product carbon footprints (PCFs) are largely unknown, leaving questions about their sustainability. This general lack of PCF data is because the data needed for comprehensive environmental analyses are typically not available in the early molecular design stages. Several predictive tools have been developed to estimate the PCF of chemicals, which are applicable to only a narrow range of common chemicals and have limited predictive ability.

Rectovaginal Fistula From Untreated Ulcerative Colitis in Pregnancy: A Case Report and Review of the Literature.

Inflammatory bowel disease can have reproductive consequences depending on disease severity at the time of conception and antepartum management. A 37-year-old G1 with ulcerative pancolitis initially did not disclose her medical history to the obstetrics providers. She developed worsening hematochezia and microcytic anemia and declined antepartum treatment of ulcerative colitis.

Stopping continuing long-term mepolizumab treatment in severe eosinophilic asthma (COMET study).

Background: The long-term efficacy and safety of mepolizumab for treatment of severe eosinophilic asthma are well established. Here, we examine the clinical impact of stopping mepolizumab after long-term use.

Methods: COMET (NCT02555371) was a randomised, double-blind, placebo-controlled, parallel-group, multicentre study.

Mepolizumab for Eosinophil-Associated COPD: Analysis of METREX and METREO.

Background: A pre-specified meta-analysis of individual patient data from the 52-week METREX and METREO trials, which investigated mepolizumab for chronic obstructive pulmonary disease (COPD) in patients with blood eosinophil counts ≥150 cells/µL (screening) or ≥300 cells/µL (prior year) and frequent exacerbations, enables more robust characterization of mepolizumab efficacy in COPD and exploration of the relationship between blood eosinophil count and treatment responses.

Methods: In METREX (117106/NCT02105948) and METREO (117113/NCT02105961), randomized patients received mepolizumab or placebo added to existing inhaled corticosteroid (ICS)-based triple maintenance therapy. The annual rate of moderate/severe exacerbations (primary endpoint) was compared between subcutaneous (SC) mepolizumab 100 mg versus placebo (primary comparison of interest) and all doses (100 mg and 300 mg SC) versus placebo in patients with blood eosinophil counts ≥150 cells/µL at screening or ≥300 cells/µL in the prior year.

Impact of baseline clinical asthma characteristics on the response to mepolizumab: a post hoc meta-analysis of two Phase III trials.

Background: Severe asthma is associated with a broad range of phenotypes and clinical characteristics. This analysis assessed whether select baseline patient characteristics could prognosticate mepolizumab efficacy in severe eosinophilic asthma.

Methods: This was a post hoc meta-analysis of data from the Phase III MENSA (NCT01691521/MEA115588) and MUSCA (NCT02281318/200862) studies.

Mepolizumab improves clinical outcomes in patients with severe asthma and comorbid conditions.

Background: Comorbidities can complicate the management of severe asthma; therefore, the presence of comorbid conditions or traits often need to be considered when considering treatment options for patients with severe asthma. The aim of this analysis is to investigate the efficacy of mepolizumab in patients with severe eosinophilic asthma and comorbidities.

Methods: This was a post hoc analysis (GSK ID:209140) of data from the Phase IIb/III studies DREAM, MENSA, SIRIUS, and MUSCA.

Clinical Development of Mepolizumab for the Treatment of Severe Eosinophilic Asthma: On the Path to Personalized Medicine.

The development of mepolizumab, an anti-IL-5 monoclonal antibody for the treatment of severe eosinophilic asthma, is an example of a clinical development program that evolved over time based on sound, basic scientific principles. Initial clinical data on the effects of mepolizumab on lung function in a general asthmatic population were disappointing. However, it became clear that mepolizumab may be more effective against other clinical endpoints, particularly asthma exacerbations, in patients with more severe disease.

Multinational cohort study of mortality in patients with asthma and severe asthma.

Background: Data on the risk of death following an asthma exacerbation are scarce. With this multinational cohort study, we assessed all-cause mortality rates, mortality rates following an exacerbation, and patient characteristics associated with all-cause mortality in asthma.

Methods: Asthma patients aged ≥18 years and with ≥1 year of follow-up were identified in 5 European electronic databases from the Netherlands, Italy, UK, Denmark and Spain during the study period January 1, 2008-December 31, 2013.

Incidence, risk factors and re-exacerbation rate of severe asthma exacerbations in a multinational, multidatabase pediatric cohort study.

Background: There are sparse real-world data on severe asthma exacerbations (SAE) in children. This multinational cohort study assessed the incidence of and risk factors for SAE and the incidence of asthma-related rehospitalization in children with asthma.

Methods: Asthma patients 5-17 years old with ≥1 year of follow-up were identified in six European electronic databases from the Netherlands, Italy, the UK, Denmark and Spain in 2008-2013.

Baseline blood eosinophil count as a predictor of treatment response to the licensed dose of mepolizumab in severe eosinophilic asthma.

Background: Previous analyses examining the relationship between blood eosinophil count and mepolizumab treatment effects in severe eosinophilic asthma have used a range of doses and administration routes.

Methods: This post hoc meta-analysis included data from the MENSA (MEA115588/NCT01691521) and MUSCA (200862/NCT02281318) trials. Patients (≥12 years) with severe eosinophilic asthma who experienced ≥2 exacerbations in the prior year received either mepolizumab 100 mg subcutaneously (SC) or 75 mg intravenously, or placebo plus standard of care every 4 weeks.

Efficacy of add-on mepolizumab in adolescents with severe eosinophilic asthma.

Adolescents (12-17 years of age) with severe eosinophilic asthma experience frequent exacerbations and reduced lung function leading to poor health-related quality of life. Mepolizumab is approved for add-on maintenance therapy in patients with severe eosinophilic asthma ≥ 6 years of age in the EU and ≥ 12 years of age in other regions (including the USA), based on a Phase II/III program demonstrating reduced exacerbation rates with 4-weekly treatment. A total of 34 adolescent patients were recruited across the Phase III mepolizumab trials.

Subcutaneous mepolizumab in children aged 6 to 11 years with severe eosinophilic asthma.

Objectives: There are no published reports for anti-interleukin-5 therapy in children <12 years with asthma. The primary objective of this study was to characterize the pharmacokinetics and pharmacodynamics of mepolizumab following subcutaneous (SC) administration in children 6 to 11 years-of-age with severe eosinophilic asthma.

Hypothesis: Mepolizumab SC pharmacokinetics and pharmacodynamics in children with severe eosinophilic asthma are comparable with adults.

Long-term Safety and Clinical Benefit of Mepolizumab in Patients With the Most Severe Eosinophilic Asthma: The COSMEX Study.

Purpose: The goal of this study was to assess the long-term safety and efficacy of mepolizumab in patients with the most severe eosinophilic asthma.

Methods: This multicenter, open-label, long-term, Phase IIIb study (COSMEX [COSMOS Extension]; 201312/NCT02135692) enrolled patients from the 52-week, open-label extension study COSMOS (A Study to Determine Long-term Safety of Mepolizumab in Asthmatic Subjects) that previously enrolled patients from the double-blinded, placebo-controlled Phase III studies MENSA (Mepolizumab as Adjunctive Therapy in Patients with Severe Asthma) and SIRIUS (Steroid Reduction with Mepolizumab Study). To enter COSMEX, patients had to have life-threatening/seriously debilitating asthma before entering MENSA or SIRIUS and to have completed these previous studies with demonstrated improvement while receiving mepolizumab.

Long-term safety and pharmacodynamics of mepolizumab in children with severe asthma with an eosinophilic phenotype.

Background: Mepolizumab is approved for patients with severe asthma with an eosinophilic phenotype aged 12 or more (United States) or 6 or more (European Union) years, but its long-term use in children aged 6 to 11 years has not yet been assessed.

Objective: We sought to assess the long-term safety, efficacy, and pharmacodynamics of mepolizumab in children aged 6 to 11 years with severe asthma with an eosinophilic phenotype.

Methods: In this open-label, uncontrolled, repeat-dose extension study (NCT02377427), children aged 6 to 11 years with severe asthma with an eosinophilic phenotype (blood eosinophil counts ≥150 cells/μL at screening or ≥300 cells/μL in the previous year) received a body weight-dependent dose of subcutaneous mepolizumab of 40 mg (<40 kg) or 100 mg (≥40 kg) over 52 weeks.

Mepolizumab reduces exacerbations in patients with severe eosinophilic asthma, irrespective of body weight/body mass index: meta-analysis of MENSA and MUSCA.

Background: We assessed the efficacy of the licensed mepolizumab dose (100 mg subcutaneously [SC]) in patients with severe eosinophilic asthma according to body weight/body mass index (BMI).

Methods: This was a post hoc individual patient-level meta-analysis of data from the Phase 3 studies MENSA (MEA115588/NCT01691521) and MUSCA (200862/NCT02281318). Patients aged ≥12 years with severe eosinophilic asthma and a history of exacerbations were randomised to 4-weekly placebo, mepolizumab 75 mg intravenously (IV) or 100 mg SC (MENSA) or placebo or mepolizumab 100 mg SC (MUSCA) for 32 (MENSA) or 24 (MUSCA) weeks.

The Pharmacokinetics and Relative Bioavailability of Mepolizumab 100 mg Liquid Formulation Administered Subcutaneously to Healthy Participants: A Randomized Trial.

This study compared the pharmacokinetic (PK) profile of a new liquid formulation of mepolizumab with the established lyophilized formulation. In this open-label, parallel-group, single-dose study (NCT03014674; GSK ID: 204958), healthy participants were randomized (1:1:1) to receive a single mepolizumab dose (100 mg) administered subcutaneously as liquid in a single-use prefilled syringe or single-use prefilled autoinjector, or as a lyophilized formulation. Maximum plasma concentration, area under the plasma concentration-time curve from time zero (predose) to time of last quantifiable concentration (AUC ), and AUC from time zero to infinity (AUC ) as well as additional PK parameters, safety assessments, and blood eosinophil count were evaluated.

No genetic associations with mepolizumab efficacy in COPD with peripheral blood eosinophilia.

Introduction: Improved understanding of genetic effects on response to treatments with novel approaches for COPD with peripheral blood eosinophilia, such as mepolizumab (a humanized monoclonal antibody to IL-5), may improve treatment outcomes. We conducted a study to identify genetic variants associated with efficacy of mepolizumab COPD.

Materials And Methods: Using generalized linear and logistic regression models, genome-wide association analyses were performed to investigate genetic associations with frequency of moderate and/or severe COPD exacerbations in COPD subjects receiving mepolizumab (weeks 0-52).

Impact of exacerbations on St George's Respiratory Questionnaire score in patients with severe asthma: post hoc analyses of two clinical trials and an observational study.

To assess the effect of asthma exacerbations and mepolizumab treatment on health status of patients with severe asthma using the St George's Respiratory Questionnaire (SGRQ). Post hoc analyses were conducted using data from two randomized controlled trials in patients ≥12 years old with severe eosinophilic asthma randomized to receive placebo or mepolizumab 75 mg intravenously (32-week MENSA study) or 100 mg subcutaneously (MENSA/24-week MUSCA studies), and an observational single-visit study in patients with severe asthma (IDEAL). Linear regression models assessed the impact of historical exacerbations on baseline SGRQ total and domain scores (using data from each of the three studies), and within-study severe exacerbations and mepolizumab treatment on end-of-study SGRQ scores (using data from MENSA/MUSCA).

Usability of mepolizumab single-use prefilled autoinjector for patient self-administration.

To evaluate usability of mepolizumab as a liquid drug product self-administered via a single-use prefilled autoinjector (AI) by patients with severe eosinophilic asthma (SEA), or their caregivers, in-clinic and at home. This open-label, single-arm, Phase IIIa study (NCT03099096; GSK ID: 204959) included patients aged ≥12 years with SEA who were either receiving mepolizumab (100 mg subcutaneously [SC]) every 4 weeks (Q4W) for ≥12 weeks before screening or not receiving mepolizumab but met criteria indicative of SEA. Patients/caregivers self-administered mepolizumab (100 mg SC) via an AI Q4W for 12 weeks.

Oral corticosteroid dose changes and impact on peripheral blood eosinophil counts in patients with severe eosinophilic asthma: a post hoc analysis.

Background: An inverse relationship between oral corticosteroid (OCS) dose and peripheral blood eosinophil (PBE) count is widely recognized in patients with severe eosinophilic asthma; however, there are limited data available to quantify this relationship. This post hoc analysis of the SIRIUS study (NCT01691508) examined the impact of weekly incremental OCS dose reductions on PBE counts during the 3-8-week optimization phase of the study.

Methods: SIRIUS was a randomized, double-blind study involving patients with severe asthma (≥12 years old), which included an initial OCS dose optimization phase prior to randomization.

Disease burden and efficacy of mepolizumab in patients with severe asthma and blood eosinophil counts of ≥150-300 cells/μL.

Background: In patients with severe eosinophilic asthma, treatment decisions can be determined by blood eosinophil counts; however, a specific blood eosinophil threshold has not been defined for starting mepolizumab treatment.

Methods: We summarized the disease burden and efficacy of mepolizumab in patients with severe eosinophilic asthma and baseline blood eosinophil counts of ≥150-300 cells/μL and ≥300 cells/μL using data from the mepolizumab clinical development program (DREAM [NCT01000506], MENSA [NCT01691521], SIRIUS [NCT01691508] and MUSCA [NCT02281318]).

Results: The morbidity of asthma in patients with baseline blood eosinophil counts ≥150-300 cells/μL was similar to that in patients with blood eosinophil counts ≥300 cells/μL, with similar rates of exacerbations (2.